基于TP53突变型胃癌患者DAXX表达特征的预后模型及其对临床结局的预测价值

doi:10.12056/j.issn.1006-2785.2024.46.12.2024-112

科研成果详情

题名	基于TP53突变型胃癌患者DAXX表达特征的预后模型及其对临床结局的预测价值
其他题名	Prognostic model based on DAXX expression in gastric cancer patients with TP53 mutation and its predictive value for clinical outcomes
作者	黄京京1; 毛亮亮 2; 林康明 1; 陈琛斌 3; 赵志光1
发表日期	2024
发表期刊	浙江医学影响因子和分区
语种	中文
原始文献类型	学术期刊
关键词	TP53突变死亡结构域相关蛋白胃癌亚细胞定位预后
其他关键词	TP53 mutation ; Death domain-associated protein ; Gastric cancer ; Subcellular localization ; Prognosis
摘要	目的分析TP53突变型胃癌(GC)患者死亡结构域相关蛋白(DAXX)表达特征并构建预后模型,评价该模型对GC患者预后的预测价值。方法收集癌症基因组图谱数据库中TP53野生型和突变型GC患者的DNA变异特征;收集2014年1月至2016年12月温州医科大学附属第一医院手术切除的GC标本,并通过免疫组化检测p53蛋白表达状态和DAXX的亚细胞定位。绘制生存曲线分析不同DAXX表达状态TP53突变型GC患者的生存差异。采用Cox比例风险回归模型评估TP53突变型GC患者DAXX细胞核表达水平及不同临床病理特征对患者预后的预测效能,建立可视化临床预后模型。结果GC患者的TP53突变主要集中于p53 DNA结合区域,且与肌联蛋白基因、低密度脂蛋白受体相关蛋白1B基因和丝聚蛋白基因的突变水平有关。与TP53野生型GC患者相比,TP53突变型GC患者DAXX的mRNA表达显著升高(P《0.05)。免疫组化分析结果显示,与TP53野生型GC患者相比,TP53突变型GC患者DAXX细胞质表达显著下降,细胞核表达显著升高,核质比显著升高,差异均有统计学意义(均P《0.01)。生存分析结果显示,在TP53突变型GC患者中,DAXX高表达,尤其是DAXX细胞核高表达提示预后良好。单因素和多因素Cox回归分析结果显示,年龄》67岁、肿瘤分期Ⅲ期、DAXX细胞核低表达是影响TP53突变型GC患者预后的独立危险因素(均P《0.10)。基于这3个指标建立的预后模型能准确预测TP53突变型GC患者的预后;模型一致性指数为0.740,显示出良好的预测效能。结论DAXX细胞核表达联合年龄、分期等临床病理特征,可较好地预测TP53突变型GC患者的预后。
其他摘要	Objective To construct a prognosis model for gastric cancer(GC)patients with TP53 mutation based on death domain-associated protein(DAXX)expression,and to evaluate its predictive values.Methods The DNA variation characteristics of GC patients with wild-type and mutant TP53 were obtained from The Cancer Genome of Atlas(TCGA)database.The specimens of GC patients operated in the First Affiliated Hospital of Wenzhou Medical University from January 2014 to December 2016 were collected.The expression of p53 protein and DAXX protein were detected by immunohistochemistry.The survival of TP53 mutant GC patients with different DAXX expression status was analyzed.The influencing factors for survival of GC patients with mutant TP53 were analyzed by univariate and multivariate Cox analysis.Based on the prognostic factors a visual clinical prediction model was established and evaluated.Results The information from TCGA database showed that TP53 mutation was mainly concentrated in p53 DNA binding region and was closely related to the mutation level of titin,low-density lipoprotein receptor-related protein 1B and filaggrin in GC patients.The mRNA expression of DAXX was significantly increased in patients with TP53 mutation(P＜0.05).Immunohistochemical analysis showed that the cytoplasmic expression of DAXX in GC patients with TP53 mutation was significantly decreased(P＜0.01),while the nuclear expression and the nuclear-cytoplasmic ratio were significantly increased(all P＜0.01).The results of survival analysis showed that the prognosis of GC patients with TP53 mutation was relatively poor;however,the high expression of DAXX,especially in the nucleus,suggests a good prognosis in GC patients with TP53 mutation.The univariate and multivariate Cox analysis showed that in patients with TP53 mutation,age＞67,tumor stage was Ⅲ,and the low expression of DAXX in the nucleus were risk factors for the prognosis(all P＜0.10).The prediction model based on these three indicators may predict the prognosis of GC patients,the C index of the model was 0.740,indicating a good prediction value.Conclusion Based on DAXX nuclear expression and age,stage,and other clinicopathological features,the clinical prognosis of GC patients with TP53 mutation can be predicted.
资助项目	浙江省医药卫生科技计划项目(2019KY459)。
ISSN	1006-2785
卷号	46 期号:12 页码:1252-1257
DOI	10.12056/j.issn.1006-2785.2024.46.12.2024-112
页数	7
收录类别	维普 ; CNKI ; 万方 ; ISTIC
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引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/215515
专题	附属第二医院附属第一医院第二临床医学院、附属第二医院、育英儿童医院附属第一医院_胃肠外科附属第二医院_病理科其他_附属第三医院（瑞安市人民医院）
通讯作者	赵志光
作者单位	1.温州医科大学附属第二医院(育英儿童医院)病理科,325024; 2.温州医科大学附属第三医院病理科; 3.温州医科大学附属第一医院胃肠外科
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 病理科
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	黄京京,毛亮亮,林康明,等. 基于TP53突变型胃癌患者DAXX表达特征的预后模型及其对临床结局的预测价值[J]. 浙江医学,2024,46(12):1252-1257.
APA	黄京京, 毛亮亮, 林康明, 陈琛斌, & 赵志光. (2024). 基于TP53突变型胃癌患者DAXX表达特征的预后模型及其对临床结局的预测价值. 浙江医学, 46(12), 1252-1257.
MLA	黄京京,et al."基于TP53突变型胃癌患者DAXX表达特征的预后模型及其对临床结局的预测价值".浙江医学 46.12(2024):1252-1257.